In this study, the effects of various nephrotoxins (e.g., organic solvents, heavy metals, antibiotics) and certain experimental manipulations will be examined for their effects on renal and nonrenal transport processes. The nephrotoxins will be studied in an attempt to determine whether or not their action is a direct one. Mainly in vitro procedures will be used with the toxins administered to the animals (rats, rabbits) prior to the experiments, as well as added directly to renal slice or homogenate preparations. Renal slices will be tested for their ability to reaccumulate inorganic electrolytes after leaching and to maintain a normal electrolyte distribution and tissue water content after exposure to nephrotoxins. Renal slice uptake of organic acids, organic bases and model amino acids will also be studied. Also the effects of abrupt interruption of renal blood flow will be examined for its effect on these various transport systems. Additionally, the subcellular distribution of various nephrotoxins will be studied. This will involve standard fractionation techniques and may help develop a better understanding of mechanisms of action through finding potential sites of action. BIBLIOGRAPHIC REFERENCES: Berndt, W. O. Dichromate nephrotoxicity and renal dichromate accumulation. Abstracts of Papers, Society of Toxicology, 14th Annual Meeting, p. 113, 1975. Koschier, Francis and W. O. Berndt. In vitro uptake of organic ions by renal cortical tissue of rats treated chronically with 2,4,5-trichlorophenoxyacetic acid. Fed. Proc. 34: 246, 1975.